Ding, YuxuanPedersen, Simon S.Lin, AlexQian, RuoyuBall, Zachary T.2022-12-132022-12-132022Ding, Yuxuan, Pedersen, Simon S., Lin, Alex, et al.. "Direct formation and site-selective elaboration of methionine sulfoximine in polypeptides." <i>Chemical Science,</i> 13, (2022) Royal Society of Chemistry: 14101-14105. https://doi.org/10.1039/D2SC04220G.https://hdl.handle.net/1911/114094Sulfoximines are emerging moieties for medicinal and biological chemistry, due in part to their efficacy in selective inhibition of amide-forming enzymes such as γ-glutamylcysteine synthetase. While small-molecule sulfoximines such as methionine sulfoximine (MSO) and its derivatives are well studied, structures with methionine sulfoximine residues within complex polypeptides have been generally inaccessible. This paper describes a straightforward means of late-stage one-step oxidation of methionine residues within polypeptides to afford NH-sulfoximines. We also present chemoselective subsequent elaboration, most notably by copper(II)-mediated N–H cross-coupling at methionine sulfoximine residues with arylboronic acid reagents. This development serves as a strategy to incorporate diverse sulfoximine structures within natural polypeptides, and also identifies the methionine sulfoximine residue as a new site for bioorthogonal, chemoselective bioconjugation.engThis Open Access Article is licensed under a Creative Commons Attribution-Non Commercial 3.0 Unported LicenceJournal articled2sc04220ghttps://doi.org/10.1039/D2SC04220G